Injecting instructions using intracortical microstimulation in association cortex

项目摘要： 努力开发神经修复装置，为失去视力的患者恢复功能， 听觉或躯体感觉通常旨在刺激神经系统的感觉通路， 以密切模仿其正常功能的方式。然而，众所周知的失聪患者人工耳蜗植入， 即使受试者的大脑必须适应人工刺激，学习解释， 声音和区别性的讲话。仿生刺激感觉通路是唯一的方法 神经假体输入到神经系统 在初步研究中，我们最近发现，受试者可以学习解释皮质内的 微刺激（ICMS）通过运动前皮层（PM）中的4个不同电极之一传递， 执行4个任意关联运动中的1个的指令。即使在PM中的ICMS被认为不 唤起感官知觉，受试者学会使用PM-ICMS指令，电流和频率太低， 引起任何肌肉收缩或运动。此外，在将电极分配给运动之后， 随机洗牌的受试者重新学习了这项任务，表明低振幅ICMS并不只是使 受试者执行特定的运动，而是诱发感知或其他经验， 能够区分并学会将其解释为指令。 在这里，我们建议调查是否受试者可以体验，区分和学习解释低- 通过额叶和顶叶的其他选定区域中的不同单电极递送的振幅ICMS 仅间接接收感觉信息的联合皮层。在目标1中，我们将检查5个额叶区域： 辅助运动区、额叶眼区、背外侧和腹外侧前额叶皮质，以及 背侧前扣带皮层在目标2中，我们将检查5个顶叶区域： 区域（顶叶到达区域）、外侧顶叶内区域、前顶叶内区域和区域7a。在目标3 我们将确定受试者是否能够学会解释这些额叶和顶叶区域的ICMS，而不仅仅是 指示，但作为反馈。这项工作的结果将扩大可供使用的领土， 实质上将人工输入传递到神经系统。神经修复装置可以被开发出来 使用这些输入来帮助受各种中枢和外周疾病影响的患者， 神经系统疾病，包括视力丧失、感觉神经元病、中风和多发性硬化。

Project Summary: Efforts to develop neuroprosthetic devices that restore function for patients who have lost vision, hearing, or somatic sensation typically aim to stimulate the sensory pathways of the nervous system in a manner that mimics their normal function closely. Yet the well-known cochlear implant for deaf patients has been successful even though the subject’s brain must adapt to the artificial stimulation, learning to interpret sounds and discriminate speech. Is biomimetic stimulation of sensory pathways the only way to provide neuroprosthetic inputs to the nervous system? In preliminary studies, we recently found that subjects could learn to interpret intracortical microstimulation (ICMS) delivered through 1 of 4 different electrodes in the premotor cortex (PM) as instructions to perform 1 of 4 arbitrarily associated movements. Even though ICMS in PM is not thought to evoke sensory percepts, subjects learned to use PM-ICMS instructions at currents and frequencies too low to evoke any muscle contraction or movement. Moreover, after the assignment of electrodes to movements was shuffled randomly subjects relearned the task, indicating that low-amplitude ICMS did not simply bias the subjects to perform specific movements, but instead evoked percepts or other experiences that the subjects could distinguish and learned to interpret as instructions. Here we propose to investigate whether subjects can experience, distinguish and learn to interpret low- amplitude ICMS delivered through different single electrodes in other select areas of the frontal and parietal association cortex that receive sensory information only indirectly. In Aim 1 we will examine 5 frontal areas: the supplementary motor area, the frontal eye field, the dorsolateral and ventrolateral prefrontal cortex, and the dorsal anterior cingulate cortex. In Aim 2 we will examine 5 parietal areas: area 5, the medial intraparietal area (parietal reach region), the lateral intraparietal area, the anterior intraparietal area, and area 7a. In Aim 3 we will determine whether subjects can learn to interpret ICMS in these frontal and parietal areas not only as instructions, but alternatively as feedback. The results of this work will expand the territory available for delivering artificial inputs to the nervous system substantially. Neuroprosthetic devices then may be developed that use such inputs to help patients affected by a wide variety of diseases of the central and peripheral nervous system including visual loss, sensory neuronopathies, stroke, and multiple sclerosis.